The invention relates to antifingal and antibacterial peptides.
Bacterial and fungal infections are prevalent and, in some cases, life-threatening conditions that affect otherwise healthy patients. Bacterial and fungal infections are especially dangerous for immuno-compromised patients. For these patients, systemic fungal infections can lead to death, since there are few safe and effective antifungal pharmaceuticals for intravenous use. Similarly, infections with various bacterial species can cause sever disease states and even death.
Although several antifungal agents (e.g., clotrimazole, miconazole, ketoconazole, and nystatin) and antibacterial agents (e.g., penicillin, streptomycin, tetracycline, and chlorhexidine) are currently available, these agents are not completely effective. These agents can also lead to drug resistant organisms and can produce adverse side effects. In addition, many are not appropriate for oral or systemic administration.
The invention features substantially pure peptides containing between 13 and 20 amino acids, inclusive; the peptides have the amino acid sequence: R1-R2-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-R17-R18-R19-R20-R21-R22-R23, where R1 is Asp or is absent; R2 is Ser or is absent; R3 is His or is absent; R4 is Ala; R5 is Lys, Gln, Arg, or another basic amino acid; R6 is Arg, Gln, Lys, or another basic amino acid; R7 is His, Phe, Tyr, Leu, or another hydrophobic amino acid; R8 is His, Phe, Tyr, Leu, or another hydrophobic amino acid; R9 is Gly, Lys, Arg, or another basic amino acid; R10 is Tyr; R11 is Lys, His, Phe, or another hydrophobic amino acid; R12 is Arg, Gln, Lys, or another basic amino acid; R13 is Lys, Gln, Arg, another basic amino acid, or is absent; R14 is Phe or is absent; R15 is His, Phe, Tyr, Leu, another hydrophobic amino acid, or is absent; R16 is Glu or is absent; R17 is Lys or is absent; R18 is His or is absent; R19 is His or is absent; R20 is Ser or is absent; R21 is His or is absent; R22 is Arg or is absent; and R23 is Gly or is absent; where Gln cannot simultaneously occupy positions R5, R6, R12, and R13 of the amino acid sequence of a peptide.
In preferred peptides, at least one of R7, R8, R11, and R15 is Phe; R9 is Lys; R11 is His; or at least one of R7, R8, and R15 is Tyr; or any combination of these substitutions is present in the peptide. In other preferred peptides, R1, R2, and R3 are absent; alternatively, R22 and R23 are absent; R20, R21, R22, and R23 are absent; or R18, R19, R20, R21, R22, and R23 are absent.
The peptides may have substituents bonded to either terminus of the peptide. For example, the peptide may have an acetyl or a carbamyl addition at the N-terminus, and/or an amide addition at the C-terminus.
Preferred peptides contain 13-16 amino acids, and more preferably contain 13-14 amino acids. The invention further features pharmaceutical compositions including the peptides of the invention.
The peptides of the present invention have potent antibacterial and antifungal properties, and the invention also features methods for treating bacterial and fungal infections using these peptides.
Other features and advantages of the invention will be apparent from the following description and from the claims.